Changes in Fertility after Exposure of Sperm to Exogenous PAF

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By Julia Robison, Slee Yi, and William E. Roudebush
PAF Audio File
 

In order to understand the concept of male fertility, a basic understanding of two processes is required. Sperm must undergo a series of steps toward maturation. The next to last step in this series is called capacitation. This typically occurs in the female’s uterus after the sperm has been ejaculated, and prepares sperm for binding with the female egg.1 Once sperm reaches the egg, it must then be able to penetrate its outer membrane – the zona pellucida2 The acrosome (a structure found around the head of the sperm) releases enzymes that break down the zona pellucida and facilitate penetration.1 This process is called the acrosome reaction. In males, fertility requires that an appropriate number of normal sperm be produced, and that these sperm be capable of undergoing both capacitation and the acrosome reaction in order to fertilize the egg and produce a pregnancy.2 Additionally, sperm motility has been identified as a principal factor in sperm function and potential for achieving fertilization.3 Infertility can result from a number of different abnormalities. However, abnormalities occurring in sperm can prevent either or both of the processes afore mentioned.

A number of endogenous factors have been attributed to regulate the fertility potential and motility of the spermatozoa, for example platelet-activating factor. Platelet-activating factor (PAF) is a unique and novel signaling phospholipid that has many different and varying biological properties in addition to platelet activation. Since its discovery in the early 1970's this novel compound has been implicated in a variety of reproductive functions including fertilization, implantation and parturition.4,5

Platelet Activating Factor

Platelet-activating factor, or PAF, is a phospholipid. In other words, it is a molecule that has a fat component and a phosphate group and makes up cell membranes. PAF was discovered around 30 years ago; it is found in many mammalian species, including in humans. This phospholipid is present in many cell types and has been shown to have a diversity of effects in addition to platelet activation.2 The name of PAF is a misleading because it causes people to associate the molecule with blood platelets. In reality, it was first observed in platelets and that is where its name comes from. PAF is of  great interest in the study of reproduction due to its important effects on fertility and pregnancy, and more specifically, its effects on sperm in respect to motility, capacitation, and the acrosome reaction. One of the places in which PAF is produced is human sperm. Although its exact mechanism of action is yet unclear, PAF is shown to positively correlate with sperm motility and ability to fertilize the female egg.2

Studies indicate that sperm contain PAF receptors in their membrane.  The distribution of these receptors throughout the sperm membrane is not uniform, and different binding sites are shown to produce different results.6 For instance, binding of PAF to receptors at the sperm cell’s midpiece will increase motility. The binding of PAF to its receptor at yet another location results in an increase of intracellular levels of calcium, triggering the acrosome reaction.7 It is further understood that PAF receptors can equally bind to PAF antagonists. When PAF successfully binds to its midpiece receptor, it increases sperm motility. Conversely, when PAF antagonists bind to these receptors, preventing PAF itself from binding, sperm motility is negatively affected. The suggestion that sperm have PAF receptors allows for the assumption that a receptor-related type of subfertility or infertility exists when receptors are abnormally distributed or absent.2 PAF and its interactions with sperm membrane receptors are worthy of review and further research.  This leads us to the hypothesis that adding exogenous/synthetic/artificial PAF to sperm sample will improve sperm function, resulting in higher pregnancy rates.

Exogenous exposure to PAF

Sperm can be treated with exogenous PAF for improved outcomes in intrauterine insemination (IUI) as well as in-vitro fertilization (IVF).  Wild and Roudebush conducted the original PAF-IUI study comparing 60 men with normal semen specimens, who were preparing to undergo IUI. Half of the men had their semen exposed to PAF for 15 minutes while the other half was not exposed. The PAF-exposed group exhibited a 46.7% pregnancy rate compared with the unexposed group, which had only a 16.7% pregnancy rate.8  Sperm treatments with PAF have produced similar results in other studies.9,10 Treatment with exogenous PAF causes sperm motility to rise, thus improving the quality of the sperm.  However, it is important to note that PAF treatment is shown to improve the performance of normal, motile sperm only.11,12 As explained above, PAF must bind to receptors on the sperm membrane in order to produce effects. Those sperm that have defective receptors will not respond to PAF treatment. This eliminates the concern that abnormal sperm cells might penetrate the egg as a result of PAF-induced motility.  Although the PAF treatment of sperm has been used and shown to be successful in human IUI procedures, there is a great potential for the use of this treatment in human IVF procedures. PAF treatment in IVF procedures has been studied in animals, where success was noted and even the quality of the embryos was improved.13,14

 

 

Summary

PAF plays an important role in human reproduction. It is produced in human sperm and acts on sperm cell membranes, causing several effects. One of the major effects is the marked increase in sperm motility. Treatment of sperm with exogenous PAF is shown to increase success rates of IUI procedures. There is great potential for the use of PAF treatment in IVF. Further research should be conducted in order to explore the potential use of PAF in other clinical applications including IVF.

INCIID gratefully thanks and acknowledges the:

1University of South Carolina School of Medicine Greenville, 2Fertility Center of the Carolinas, and

Department of Obstetrics & Gynecology, Greenville Health System, Greenville, South Carolina

 

 

 

References

  1. Davis BK. Timing of fertilization in mammals: Sperm cholesterol/phospholipid radio as a determinant of the capacitation interval. PNAS(USA) 1981;78:7560-7564.
  2. Roudebush WE. Seminal platelet-activating factor. Sem Thromb Hemost 2007;33:69-74.
  3. Roudebush WE, Purnell ET. Platelet-activating factor content in human spermatozoa and pregnancy outcome. Fertil Steril 2000;74:257-260.
  4. Harper MJK. Platelet activating factor: a paracrine factor in 
preimplantation stages of development. Biol Reprod 1989;40: 907–913
  5. Roudebush WE, Diehl JR. Platelet-activating factor content in boar spermatozoa correlates with fertility. Therio 2001;55:1633–1638.
  6. Sathananthan AH, Ratnam SS, Ng SC, et al. The sperm centriole: Its inheritance, replication and perpetuation in early human embryos. Hum Reprod 1996;11:345-356.
  7. Benoff N. Modeling human-sperm interactions in vitro: Signal transduction pathways regulating the acrosome reaction. Mol Hum Reprod 1998;4:453-471.
  8. Wild MD, Roudebush WE. Platelet-activating factor improves intrauterine insemination success. Amer J Obstet Gynecol 2001;184:1064-1065.
  9. Roudebush WE, Massey JB, Toledo AA, et al. Platelet-activating factor significantly enhances intrauterine insemination pregnancy rates. Fertil Steril 2004;82:52-56.
  10. Grigoriou O, Makrais E, Konidaris S, et al. Effect of sperm treatment with exogenous platelet-activating factor on the outcome of intrauterine insemination. Fertil Steril 2005;83: 618-621
  11. Stavroula B, Odysseas G, Dimitris H, et al. Treatment of sperm with platelet-activating factor does not improve intrauterine insemination outcomes in unselected cases of mild male factor infertility: A prospective double-blind randomized crossover study. Urology 2009;74:1025-1028.
  12. Wang R, Sikka SC, Veeraragavan K. Platelet activating factor and pentoxifylline as human sperm cryoprotectants. Fertil Steril 1993;56:768-770.
  13.  Roudebush WE, Minhas BS, Ricker DD, Palmer TV, Dodson /SN>MG. Platelet activating factor enhances in vitro fertilization of rabbit oocytes. Am J Obstet Gynecol 1990;163:1670–1673
  14. Roudebush WE, Fukuda AI, Minhas BS. Enhanced embryo development of rabbit oocytes fertilized in vitro with platelet- activating factor (PAF) treated sperm. J Assist Reprod Genet 1993;10:91–94

 

 

Additional Resources

Briton-Jones C, Yeung QS, Tjer GC. The effects of follicular fluid and platelet-activating factor on motion characteristics of poor-quality cryopreserved human sperm. J Assisted Reprod Genet 2001;183:165-170.

Stavroula B, Odysseas G, Dimitris H, et al. Treatment of sperm with platelet-activating factor does not improve intrauterine insemination outcomes in unselected cases of mild male factor infertility: A prospective double-blind randomized crossover study. Urology 2009;74:1025-1028.

Roudebush WE, Fukuda AI, Minhas BS. Enhanced embryo development of rabbit oocytes fertilized in vitro with platelet-activating factor (PAF) treated spermatozoa. J Assisted Reprod Genet 1993;10:91-94.

Sengoku K, Ishikawa M, Tamate K, et al. Effects of platelet activating factor on mouse sperm function. J Assisted Reprod Genet 1992;9:447-453.

Zhu J, Massey M, Mitchell-Leef D, et al. Platelet-activating factor acetylhydrolase activity affects sperm motility and serves as a decapacitation factor. Fertil Steril 2006;85:391-394.

Jarvey K, Langlais J, Gagnon C. Platelet-activating factor acetylhydrolase in the male reproductive tract: Origin and properties. Internat J Androl 1993;16:121-127.

Hellstrom WJG, Wang R, Sikka SC. Platelet-activating factor stimulates motion parameters of cryopreserved human sperm. Fertil Steril 1991;56:768-770.

 

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